Alpha-Ketoglutarate Dehydrogenase Deficiency

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This disorder is caused by a problem in the Krebs cycle, an important system that helps to produce energy in your cells so that they can carry out their functions properly. This system relies on an enzyme called the Alpha-Ketoglutarate Dehydrogenase.

If you have a problem producing enough of the Alpha-Ketoglutarate Dehydrogenase enzyme, you will be unable to produce and distribute enough energy to meet the needs of your body. This causes problems in many different cells, which need a constant supply of energy to function

The prevalence of Alpha-Ketoglutarate Dehydrogenase Deficiency is currently unknown as it is an extremely rare condition. The number of cases reported appear to be less than 10.

Most cases so far have been observed in Algeria and Tunisia, suggesting that there may be a higher presence in Northern African countries.

The signs and symptoms of Alpha-Ketoglutarate Dehydrogenase Deficiency usually present soon after birth. There are a wide range of symptoms that you can present with, and some of the most common are:

• Developmental delays
• Difficulty in muscle use (hypotonia)
• Enlargement of the liver (hepatomegaly)
• The production of too much acid in the blood (metabolic acidemia and lactic acidemia)
• An increase in protein in your muscles, suggesting heart or muscle damage (increased creatine kinase levels)
• Difficulties breathing and eating, due to affected airways
• SeizuresLife expectancy is short, and most children do not live beyond early childhood.

To diagnose Alpha-Ketoglutarate Dehydrogenase Deficiency, specialised blood and urine tests are used. Your medical team may also carry out genetic tests to confirm the diagnosis.

This disorder is sometimes considered similar to Maple Syrup Urine Disease, a metabolic disorder that is part of the UK newborn screening programme.

There is currently no cure for Alpha-Ketoglutarate Dehydrogenase Deficiency. Treatment can only alleviate some of the symptoms and offer support.

A dietician will help manage your diet to ensure that your body is getting the right nutrients. Supplements and medication may also be offered. Your medical team may also recommend physical therapy to help with muscle use. It may be necessary to stay in a hospital or a hospice for the appropriate treatment and care.

Due to the complex nature of Alpha-Ketoglutarate Dehydrogenase Deficiency, prognosis is poor and many children with the disorder don’t make it past early childhood.

Alpha-Ketoglutarate Dehydrogenase Deficiency is inherited from both parents in an autosomal recessive inheritance pattern. This means that both parents are carriers of the disorder through their genes.

All genes come in pairs. Carriers of Alpha-Ketoglutarate Dehydrogenase Deficiency have one working gene and one faulty gene. Children inherit one gene from each parent to make their pair. Whether you have Fumarase Deficiency depends on the genes you inherit:

• There is a 50% chance that the child will inherit one faulty and one working gene, which means they will also be a carrier.
• There is a 25% chance that the child will inherit two working genes and not inherit or carry the faulty gene.
• There is a 25% chance that the child will inherit two faulty genes, which means they will have Alpha-Ketoglutarate Dehydrogenase Deficiency

References are available on request. Please contact us by phoning 0800 652 3181 or emailing contact@metabolicsupport.org [Resource Library No: AEM012

Please note calls to 0800 numbers are free from UK landlines and mobiles. Calls from business lines may be charged – please check with your provider.

This information about metabolic diseases is provided by Metabolic Support UK and is intended for educational purposes only. It should not be used for diagnostic or treatment purposes.

Should you require more detailed information please contact Metabolic Support UK by email (contact@metabolicsupport.org) or by telephone ( 0800 652 3181). For specific medical information regarding a disorder or individual please contact your GP or Paediatrician. Metabolic Support UK accepts no responsibility for any errors or omissions nor does Metabolic Support UK assume any liability of any kind for the content of any information contained within this summary or any use that you may make of it.